Bacterial luciferase is suggested as an enzyme which deteriorates from aberrant reactions accompanying normal catalysis. Chemical mistakes are postulated to accumulate and to cause active site heterogeneity in luciferase and possibly other enzyme molecules which undergo extensive catalytic turnover. Active site heterogeneity in the luciferase population is expected to be manifested by multiple activities and altered ligand binding properties. The source of the degradation reactions may be photodynamic processes which occur during non-emissive decay of the high energy electronic intermediate represented by the emitter of luciferase. These processes are proposed to produce enzyme modifications which result in altered binding of luciferase to flavin mononucleotide, a normal product of the enzymatic reaction. Affinity electrophoresis and affinity chromatography using immobilized flavins are proposed as methods to separate the partially or fully inactivated enzyme populations. Chemical characterization of copolymerized flavin derivatives used in the affinity methodologies is an integral component in the proposed investigation. Affinity separation of the enzyme populations containing altered ligand binding sites is envisioned as a logical first step to study the structural nature of the modifications. The accumulation of defects in bacterial luciferase caused by catalytic turnover is suggested as a molecular signal for the onset of in vivo degradation of the enzyme. This investigation may have important general implications regarding catalytic degradation in enzymes which proceed through high energy excited state intermediates.